An Ethical Analysis of Therapy for Severe Congenital Kidney and Urinary Tract Anomalies.

Technological advancements before and after delivery have greatly altered the counseling of pregnant patients facing a fetal diagnosis of severe oligohydramnios or anhydramnios secondary to congenital anomalies of the kidneys and urinary tract. Once considered a nearly uniformly lethal abnormality, long-term survival may now be possible secondary to prenatal innovations aimed at restoring the amniotic fluid volume and the availability of more advanced neonatal dialysis techniques. However, these available therapies are far from perfect. The procedures are onerous for pregnant patients without a guarantee of success, and families must prepare themselves for the complex life-long medical care that will be necessary for surviving individuals. Multidisciplinary counseling is imperative to help pregnant individuals understand the complexity of these conditions and assist them in exercising their right to informed decision-making. Moreover, as with any developing field of medicine, providers must contend with ethical questions related to the treatment options, including questions regarding patient-hood, distributive justice, and the blurred lines between research, innovation, and standard care. These ethical questions are best addressed in a multidisciplinary fashion with consideration of multiple points of view from various subspecialties. Only by seeing the entirety of the picture can we hope to best counsel patients about these highly complex situations and help navigate the most appropriate care path.

Derivation of paediatric blood pressure percentiles from electronic health records.

BACKGROUND: Identification of abnormal blood pressure (BP) in children requires normative data. We sought to examine the feasibility of using "real-world" office BP data obtained from electronic health records (EHR) to generate age-, sex- and height-specific BP percentiles for children. METHODS: Using data collected 01/01/2009-8/31/2021 from eight large children's healthcare organisations in PEDSnet, we applied a mixed-effects polynomial regression model with random slopes to generate Z-scores and BP percentiles and compared them with currently used normative BP distributions published in the 2017 American Academy of Paediatrics (AAP) Clinical Practise Guidelines (CPG). FINDINGS: We identified a study sample of 292,412 children (1,085,083 BP measurements), ages 3-17 years (53% female), with no chronic medical conditions, who were not overweight/obese and who were primarily seen for general paediatric care in outpatient settings. Approximately 45,000-75,000 children contributed data to each age category. The PEDSnet systolic BP percentile values were 1-4 mmHg higher than AAP CPG BP values across age-sex-height groups, with larger differences observed in younger children. Diastolic BP values were also higher in younger children; starting with age 7 years, diastolic BP percentile values were 1-3 mmHg lower than AAP CPG values. Cohen's Kappa was 0.90 for systolic BP, 0.66 for diastolic BP, and 0.80 overall indicating excellent agreement between PEDSnet and 2017 AAP CPG data for systolic BP and substantial agreement for diastolic BP. INTERPRETATION: Our analysis indicates that real-word EHR data can be used to generate BP percentiles consistent with current clinical practise on BP management in children. FUNDING: Funding for this work was provided by the Preserving Kidney Function in Children with Chronic Kidney Disease (PRESERVE) study; Patient-Centred Outcomes Research Institute (PCORI) RD-2020C2020338 (Principal Investigator: Dr. Forrest; Co-Principal Investigator: Dr. Denburg).

Patient-Reported Outcomes Over 24 Months in Pediatric CKD: Findings From the MyKidneyHealth Cohort Study.

RATIONALE & OBJECTIVE: The lived experience of children with chronic kidney disease (CKD) is poorly characterized. We examined the associations between patient-reported outcome (PRO) scores measuring their fatigue, sleep health, psychological distress, family relationships, and global health with clinical outcomes over time in children, adolescents, and younger adults with CKD and investigated how the PRO scores of this group compare with those of other children, adolescents, and younger adults. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 212 children, adolescentss, and adults aged 8 to 21 years with CKD and their parents recruited from 16 nephrology programs across North America. PREDICTORS: CKD stage, disease etiology, and sociodemographic and clinical variables. OUTCOME: PRO scores over 2 years. ANALYTICAL APPROACH: We compared PRO scores in the CKD sample with a nationally representative general pediatric population (ages 8 to 17 years). Change of PROs over time and association of sociodemographic and clinical variables with PROs were assessed using multivariable regression models. RESULTS: For all time points, 84% of the parents and 77% of the children, adolescents, and younger adults completed PRO surveys . The baseline PRO scores for the participants with CKD revealed a higher burden of fatigue, sleep-related impairment, psychological distress, impaired global health, and poorer family relationships compared with the general pediatric population, with median score differences≥1 SD for fatigue and global health. The baseline PRO scores did not differ by CKD stage or glomerular versus nonglomerular etiology. Over 2 years, PROs were stable with a<1-point annual change on average on each measure and intraclass correlation coefficients ranging from 0.53 to 0.79, indicating high stability. Hospitalization and parent-reported sleep problems were associated with worse fatigue, psychological health, and global health scores (all P<0.04). LIMITATIONS: We were unable to assess responsiveness to change with dialysis or transplant. CONCLUSIONS: Children with CKD experience a high yet stable burden of impairment across numerous PRO measures, especially fatigue and global health, independent of disease severity. These findings underscore the importance of assessing PROs, including fatigue and sleep measures, in this vulnerable population. PLAIN-LANGUAGE SUMMARY: Children with chronic kidney disease (CKD) have many treatment demands and experience many systemic effects. How CKD impacts the daily life of a child is poorly understood. We surveyed 212 children, adolescents, and younger adults with CKD and their parents over 24 months to assess the participants' well-being over time. Among children, adolescents, and younger adults with CKD we found a very high and persistent burden of psychological distress that did not differ by degree of CKD or type of kidney disease. The participants with CKD endorsed greater impairment in fatigue and global health compared with healthy children, adolescents, and younger adults, and parent-reported sleep problems were associated with poorer patient-reported outcome (PRO) scores across all domains. These findings emphasize the importance of including PRO measures, including fatigue and sleep measures, into routine clinical care to optimize the lived experience of children with CKD.

An initiative to improve effluent culture detection among pediatric patients undergoing peritoneal dialysis through process improvement.

BACKGROUND: Peritonitis is a significant cause of morbidity and healthcare cost among pediatric patients undergoing peritoneal dialysis. Culture-negative peritonitis has been associated with an increased risk of technique failure. Known risk factors for culture-negative peritonitis are related to the process of collection and sample processing for culture, but additional studies are needed. A culture detection rate of 16.7% was identified among our patients undergoing peritoneal dialysis, which is below the national benchmark of ≥ 85%. Our primary objective of this quality improvement project was to improve culture detection rates. METHODS: Interventions were developed aimed at standardizing the process of effluent collection and laboratory processing, timely collection and processing of samples, and addressing other modifying risk factors for lack of bacterial growth from culture. These interventions included direct inoculation of effluent into blood culture bottles at bedside and use of an automated blood culture system. Two Plan-Do-Study-Act cycles were completed prior to moving to the sustain phase. RESULTS: The culture detection rate improved from 16.7% (pre-intervention) to 100% (post-intervention). A decrease in the median process time also occurred from 83 min (pre-intervention) to 53 min (post-intervention). An individual and moving range chart identified a decrease in both the centerline (mean) and upper control limit, indicating that the process became more reliable during the sustain phase. CONCLUSIONS: An improvement in process time and culture positivity rate occurred following standardization of our PD fluid culture process. Future studies should be aimed at the impact of the components of collection and processing methods on the effluent culture yield. A higher resolution version of the Graphical abstract is available as Supplementary information.

Survival of neonates born with kidney failure during the initial hospitalization.

BACKGROUND: Survival to hospital discharge in neonates born with kidney failure has not been previously described. METHODS: This was a retrospective, observational analysis of the Pediatric Health Information System (PHIS) database from 2005 to 2019. Primary outcome was survival at discharge; secondary outcomes were hospital and ICU length of stay (LOS). Univariate analysis was performed to describe the population by birth weight (BW) and characterize survival; multivariable generalized liner mixed modeling assuming a binomial distribution and logit link was performed to identify mortality risk factors. RESULTS: Of 213 neonates born with kidney failure (median BW 2714 g; GA 35 weeks; 68% male), 4 (1.9%) did not receive dialysis or peritoneal dialysis (PD) catheter placement, 152 (72.9%) received PD only, 49 (23.4%) received PD plus extracorporeal dialysis (ECD), and 8 (3.4%) were treated with an undocumented dialysis modality. Median age at dialysis initiation was 7 days; median hospital LOS and ICU LOS were 84 and 69 days, respectively. One-hundred and sixty-two patients (76%) survived to discharge. Non-survivors (n = 51) were more likely to have received ECD and mechanical ventilation, and had a longer duration of mechanical ventilation. Every day of mechanical ventilation increased the mortality odds by 2% (n = 189; adjusted OR 1.02; 1.01, 1.03); in addition, the odds of mortality were 2 times higher in those who received ECD vs. only PD (adjusted OR 2.25; 1.04, 4.86). CONCLUSIONS: Survival to initial hospital discharge occurs in the majority of neonates born with kidney failure. Predictors of increased mortality included longer duration of mechanical ventilation, as well as the requirement for ECD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Single-Center Experience on Growth in Infants Born With End-Stage Kidney Disease.

OBJECTIVES: Children with chronic kidney disease display poor growth that impacts health outcomes; data on infants with severe congenital anomalies of the kidney and urinary tract (CAKUT) are limited. We examined growth patterns in infants with CAKUT requiring dialysis in the first 30 days. METHODS: This study evaluated infants with severe CAKUT from 2014 to 2018 surviving past 30 days. Somatic growth parameters as per standard infant curves and nutritional information were recorded. RESULTS: Twenty four infants met inclusion criteria. Seventeen infants received dialysis, demonstrating somatic growth disruption most profound at a 1-2 months postnatal age. Growth trends were improved compared to infants with CAKUT who did not require dialysis. Linear growth failed to normalize by 1 year of age. CONCLUSIONS: Infants with severe CAKUT are at high risk for early growth failure. Understanding of this deficit and impacts of early dialysis on growth and long-term outcomes are needed to identify targeted nutritional strategies.

Skeletal Outcomes in Children and Young Adults with Glomerular Disease.

BACKGROUND: Children with glomerular disease have unique risk factors for compromised bone health. Studies addressing skeletal complications in this population are lacking. METHODS: This retrospective cohort study utilized data from PEDSnet, a national network of pediatric health systems with standardized electronic health record data for more than 6.5 million patients from 2009 to 2021. Incidence rates (per 10,000 person-years) of fracture, slipped capital femoral epiphysis (SCFE), and avascular necrosis/osteonecrosis (AVN) in 4598 children and young adults with glomerular disease were compared with those among 553,624 general pediatric patients using Poisson regression analysis. The glomerular disease cohort was identified using a published computable phenotype. Inclusion criteria for the general pediatric cohort were two or more primary care visits 1 year or more apart between 1 and 21 years of age, one visit or more every 18 months if followed >3 years, and no chronic progressive conditions defined by the Pediatric Medical Complexity Algorithm. Fracture, SCFE, and AVN were identified using SNOMED-CT diagnosis codes; fracture required an associated x-ray or splinting/casting procedure within 48 hours. RESULTS: We found a higher risk of fracture for the glomerular disease cohort compared with the general pediatric cohort in girls only (incidence rate ratio [IRR], 1.6; 95% CI, 1.3 to 1.9). Hip/femur and vertebral fracture risk were increased in the glomerular disease cohort: adjusted IRR was 2.2 (95% CI, 1.3 to 3.7) and 5 (95% CI, 3.2 to 7.6), respectively. For SCFE, the adjusted IRR was 3.4 (95% CI, 1.9 to 5.9). For AVN, the adjusted IRR was 56.2 (95% CI, 40.7 to 77.5). CONCLUSIONS: Children and young adults with glomerular disease have significantly higher burden of skeletal complications than the general pediatric population.

Severe Fetal CAKUT (Congenital Anomalies of the Kidneys and Urinary Tract), Prenatal Consultations, and Initiation of Neonatal Dialysis.

INTRODUCTION: Pediatric nephrology prenatal consultations for congenital anomalies of the kidney and urinary tract (CAKUT) and criteria for kidney replacement therapy initiation in neonatal end-stage kidney disease (ESKD) are not well described. We evaluated pediatric nephrology approaches to prenatal CAKUT counseling and neonatal dialysis initiation. METHODS: A 35-question Qualtrics survey was distributed via the North American Pediatric Renal Trials and Collaborative Studies email list between January and March 2021. Thirty-nine pediatric nephrology centers completed the survey. RESULTS: All but one responding center (n = 38) provide prenatal CAKUT consultations and neonatal dialysis, with wide variability in reported multispecialty involvement. Nearly half (47%) of centers utilize written/unwritten criteria for offering neonatal dialysis. The most common contraindications to neonatal dialysis were parental refusal (61%), contraindication to access placement by surgeons (55%), and birth weight (BW) contraindication (55%, with < 1,500 g being the most common BW contraindication). Overall, 79% of centers reported caring for < 5 neonates with ESKD in the past year, 61% use hemodialysis therapies prior to peritoneal dialysis in neonates requiring dialysis, and 100% transition to peritoneal dialysis by hospital discharge. CONCLUSION: Many pediatric nephrology programs provide prenatal CAKUT consultations and neonatal dialysis, but with variability in practice approach. Further multicenter research regarding prenatal consultations and neonatal dialysis outcomes is necessary to further improve care delivery to this population.

Pregnancy associated TMA in 13-year-old patient successfully treated with Eculizumab: case report.

BACKGROUND: This report introduces an unusual cause of kidney failure in a previously healthy pediatric patient. She developed thrombotic microangiopathy (TMA) that was diagnosed post-partum, requiring dialysis and eculizumab, with eventual recovery of kidney function ([chronic kidney disease (CKD) stage 3]. CASE PRESENTATION: The patient was induced at term due to preeclampsia, with delivery complicated by severe postpartum hemorrhage from uterine atony. She continued to have severe hypertension post-delivery and further developed acute kidney injury (AKI) with decreased urinary output and respiratory distress requiring dialysis therapy. Labs revealed hemolysis with elevated lactate dehydrogenase, low haptoglobin, anemia, and thrombocytopenia, but otherwise unremarkable immunology labs. Once clinically stabilized the patient underwent kidney biopsy, which was consistent with TMA. Treatment was initiated with eculizumab, a monoclonal antibody for terminal complement blockade. Her clinical status improved (including markers of hemolysis and inflammation) with kidney replacement therapy and complement blockade. On discharge, she had increasing urine output and was prescribed 3 day per week hemodialysis and twice monthly eculizumab infusions. By 6 weeks post-delivery, hemodialysis was discontinued and her eculizumab was weaned to monthly infusions. Eculizumab was discontinued at 12 months postpartum. Genetic testing for mutations of the complement system was negative. The patient has residual stage 3 CKD with stable kidney function, requiring two agents for blood pressure control, including an ACE inhibitor for antiproteinuric effect. CONCLUSIONS: This case report showcases an unusual cause of renal failure in a pediatric patient due to TMA in the post-partum period. She required intermittent hemodialysis (iHD) for a brief period, however she was treated successfully with eculizumab that was able to be weaned off 1 year after delivery. She has residual stage 3 CKD and no further signs or symptoms of TMA.

Omentectomy reduces the need for peritoneal dialysis catheter revision in children: a study from the Pediatric Nephrology Research Consortium.

BACKGROUND: There are no multi-center studies examining omentectomy and peritoneal dialysis (PD) catheter revision in the pediatric dialysis population. METHODS: We performed a retrospective study at eight centers within the Pediatric Nephrology Research Consortium (PNRC). Data review included all incident tunneled PD catheters placed between 1/1/2011 and 12/31/2016 in pediatric stage 5 chronic kidney disease (CKD 5) patients. The primary outcome was the need for catheter revision and/or replacement. Multivariable logistic regression was performed to evaluate predictors for catheter revision/replacement. RESULTS: Data from 184 children (62.5% male; median age 7.4 years) were analyzed. Omentectomy was completed in 63.6% (n = 117). Revision/replacement occurred in 34.2% (n = 63); median time to revision/replacement was 38.5 days after insertion. PD catheter revision/replacement catheter occurred in 23.9% who underwent omentectomy versus 52.2% without omentectomy (p = 0.0005). Children ≥ 6 years at the time of catheter insertion experienced fewer revisions/replacements (18.2% age ≥ 6 vs. 56.5% age < 6 years, p <0.001). After adjusting for covariates, omentectomy reduced the need for revision by 63%; revision was 3.66 times more likely in those < 6 years of age. CONCLUSIONS: This multi-center study demonstrates that omentectomy at the time of PD catheter insertion in pediatric patients is strongly associated with reduced likelihood of PD catheter revision. Omentectomy should be considered at the time of PD catheter insertion, especially in young children who are at high risk for PD catheter malfunction. A higher resolution version of the Graphical abstract is available as Supplementary information.

A comparison of the buttonhole and rope-ladder AVF cannulation techniques and infection rates within the SCOPE collaborative.

BACKGROUND: Studies regarding hemodialysis (HD) arteriovenous fistula (AVF) cannulation in adults indicate a higher risk of infection with the buttonhole (BH) technique compared to the rope-ladder (RL) technique. Pediatric data on this issue is sparse. METHODS: We compared infection rates within the Standardizing Care to Improve Outcomes in Pediatric End stage kidney disease (SCOPE) centers performing BH cannulation versus RL cannulation of AVF. Generalized linear mixed modeling was used to assess differences in access-related blood stream infection (BSI) and access site infection (ASI) rates between the centers. RESULTS: Data was available from 211 AVF enrollments among 210 children. There were 61 AVF enrollments at 6 BH centers and 150 enrollments at 13 RL centers. Demographics were similar between the two groups. There were 12 total infections in 3383 patient months. BH centers had 3 infections (0 BSI, 3 ASI) and RL centers had 9 infections (5 BSI, 3 ASI). Mean [95% confidence interval] infection rates per 1000 patient months were not different between BH and RL centers (BH: 3.1 [0.6,15.6], RL: 3.2 [1.3,9.4], p = 0.947). A survey was also completed by the BH centers to describe their BH practices. The BH procedure at the majority of sites was characterized by a small patient/nurse ratio and strict antiseptic protocols. CONCLUSIONS: This data provides evidence of a low BSI rate associated with BH cannulation in pediatric HD patients. Further studies are needed to better delineate the differences in the pediatric and adult experience with the BH cannulation technique.

Tunneled hemodialysis catheter care practices and blood stream infection rate in children: results from the SCOPE collaborative.

OBJECTIVE: The Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) collaborative seeks to reduce hemodialysis (HD) catheter-associated blood stream infections (CA-BSI) by increasing implementation of standardized HD catheter care bundles. We report HD catheter care practices and HD CA-BSI rates from SCOPE. METHODS: Catheter care practices and infection events were collected prospectively during the study period, from collaborative implementation in June 2013 through May 2017. For comparative purposes, historical data, including patient demographics and HD CA-BSI events, were collected from the 12 months prior to implementation. Catheter care bundle compliance in 5 care bundle categories was monitored across the post-implementation reporting period at each center via monthly care observation forms. CA-BSI rates were calculated monthly, and reported as number of infections per 100 patient months. Changes in CA-BSI rates were assessed using generalized linear mixed model (GLMM) techniques. RESULTS: Three hundred twenty-five patients with tunneled HD catheters [median (IQR) age 12 years (6, 16), M 53%, F 47%] at 15 centers were included. A total of 3996 catheter care observations over 4170 patient months were submitted with a median (IQR) 5 (2, 14) observations per patient. Overall bundle compliance was high at 87.6%, with a significant and progressive increase (p < 0.001) in compliance for 4/5 bundle categories over the 48-month study period. The adjusted CA-BSI rate significantly decreased over time from 3.3/100 patient months prior to implementation of the care bundles to 0.8/100 patient months 48 months after care bundle implementation (p < 0.001). CONCLUSIONS: Using quality improvement methodology, SCOPE has demonstrated a significant increase in compliance with a majority of HD catheter care practices and a significant reduction in the rate of CA-BSI among children maintained on HD.

Using Electronic Health Record Data to Rapidly Identify Children with Glomerular Disease for Clinical Research.

BACKGROUND: The rarity of pediatric glomerular disease makes it difficult to identify sufficient numbers of participants for clinical trials. This leaves limited data to guide improvements in care for these patients. METHODS: The authors developed and tested an electronic health record (EHR) algorithm to identify children with glomerular disease. We used EHR data from 231 patients with glomerular disorders at a single center to develop a computerized algorithm comprising diagnosis, kidney biopsy, and transplant procedure codes. The algorithm was tested using PEDSnet, a national network of eight children's hospitals with data on >6.5 million children. Patients with three or more nephrologist encounters (n=55,560) not meeting the computable phenotype definition of glomerular disease were defined as nonglomerular cases. A reviewer blinded to case status used a standardized form to review random samples of cases (n=800) and nonglomerular cases (n=798). RESULTS: The final algorithm consisted of two or more diagnosis codes from a qualifying list or one diagnosis code and a pretransplant biopsy. Performance characteristics among the population with three or more nephrology encounters were sensitivity, 96% (95% CI, 94% to 97%); specificity, 93% (95% CI, 91% to 94%); positive predictive value (PPV), 89% (95% CI, 86% to 91%); negative predictive value, 97% (95% CI, 96% to 98%); and area under the receiver operating characteristics curve, 94% (95% CI, 93% to 95%). Requiring that the sum of nephrotic syndrome diagnosis codes exceed that of glomerulonephritis codes identified children with nephrotic syndrome or biopsy-based minimal change nephropathy, FSGS, or membranous nephropathy, with 94% sensitivity and 92% PPV. The algorithm identified 6657 children with glomerular disease across PEDSnet, ≥50% of whom were seen within 18 months. CONCLUSIONS: The authors developed an EHR-based algorithm and demonstrated that it had excellent classification accuracy across PEDSnet. This tool may enable faster identification of cohorts of pediatric patients with glomerular disease for observational or prospective studies.

Kidney Support in Children using an Ultrafiltration Device: A Multicenter, Retrospective Study.

BACKGROUND AND OBJECTIVES: Provision of kidney replacement therapy (KRT) to manage kidney injury and volume overload in critically ill neonates and small children is technically challenging. The use of machines designed for adult-sized patients, necessitates large catheters, a high extracorporeal volume relative to patient size, and need for blood priming. The Aquadex FlexFlow System (CHF Solutions Inc., Eden Prairie, MN) is an ultrafiltration device designed for fluid removal in adults with diuretic resistant heart failure. It has an extracorporeal volume of 33 ml, which can potentially mitigate some complications seen at onset of KRT in smaller infants. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this multicenter, retrospective case series of children who received KRT with an ultrafiltration device (n=119 admissions, 884 circuits), we report demographics, circuit characteristics, complications, and short- and long-term outcomes. Patients were grouped according to weight (<10, 10-20, and >20 kg), and received one of three modalities: slow continuous ultrafiltration, continuous venovenous hemofiltration (CVVH), or prolonged intermittent KRT. Our primary outcome was survival to end of KRT. RESULTS: Treatment patterns and outcomes varied between the groups. In patients who weighed <10 kg, the primary indication was AKI in 40%, volume overload in 46%, and ESKD in 14%. These patients primarily received CVVH (66%, n=48) and prolonged intermittent KRT (21%, n=15). In the group weighing >20 kg, volume overload was the primary indication in 91% and slow continuous ultrafiltration was the most common modality. Patients <10 kg had lower KRT survival than those >20 kg (60% versus 97%), more volume overload at onset, and received KRT for a longer duration. Cardiovascular complications at initiation were seen in 3% of treatments and none were severe. Complications during therapy were seen in 15% treatments and most were vascular access-related. CONCLUSIONS: We report the first pediatric experience using an ultrafiltration device to provide a range of therapies, including CVVH, prolonged intermittent KRT, and slow continuous ultrafiltration. We were able to initiate KRT with minimal complications, particularly in critically ill neonates. There is an unmet need for devices specifically designed for younger patients. Having size-appropriate machines will improve the care of smaller children who require kidney support.

Bortezomib in the treatment of antibody-mediated rejection in pediatric kidney transplant recipients: A multicenter Midwest Pediatric Nephrology Consortium study.

Antibody-mediated rejection leads to allograft loss after kidney transplantation. Bortezomib has been used in adults for the reversal of antibody-mediated rejection; however, pediatric data are limited. This retrospective study was conducted in collaboration with the Midwest Pediatric Nephrology Consortium. Pediatric kidney transplant recipients who received bortezomib for biopsy-proven antibody-mediated rejection between 2008 and 2015 were included. The objective was to characterize the use of bortezomib in pediatric kidney transplant recipients. Thirty-three patients received bortezomib for antibody-mediated rejection at nine pediatric kidney transplant centers. Ninety percent of patients received intravenous immunoglobulin, 78% received plasmapheresis, and 78% received rituximab. After a median follow-up of 15 months, 65% of patients had a functioning graft. The estimated glomerular filtration rate improved or stabilized in 61% and 36% of patients at 3 and 12 months post-bortezomib, respectively. The estimated glomerular filtration rate at diagnosis significantly predicted estimated glomerular filtration rate at 12 months after adjusting for chronic histologic changes (P .001). Fifty-six percent of patients showed an at least 25% reduction in the mean fluorescence intensity of the immune-dominant donor-specific antibody, 1-3 months after the first dose of bortezomib. Non-life-threatening side effects were documented in 21 of 33 patients. Pediatric kidney transplant recipients tolerated bortezomib without life-threatening side effects. Bortezomib may stabilize estimated glomerular filtration rate for 3-6 months in pediatric kidney transplant recipients with antibody-mediated rejection.

Follow-Up Renal Assessment of Injury Long-Term After Acute Kidney Injury (FRAIL-AKI).

BACKGROUND AND OBJECTIVES: Novel urinary kidney damage biomarkers detect AKI after cardiac surgery using cardiopulmonary bypass (CPB-AKI). Although there is growing focus on whether AKI leads to CKD, no studies have assessed whether novel urinary biomarkers remain elevated long term after CPB-AKI. We assessed whether there was clinical or biomarker evidence of long-term kidney injury in patients with CPB-AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a cross-sectional evaluation for signs of chronic kidney injury using both traditional measures and novel urinary biomarkers in a population of 372 potentially eligible children (119 AKI positive and 253 AKI negative) who underwent surgery using cardiopulmonary bypass for congenital heart disease at Cincinnati Children's Hospital Medical Center between 2004 and 2007. A total of 51 patients (33 AKI positive and 18 AKI negative) agreed to long-term assessment. We also compared the urinary biomarker levels in these 51 patients with those in healthy controls of similar age. RESULTS: At long-term follow-up (mean duration±SD, 7±0.98 years), AKI-positive and AKI-negative patients had similarly normal assessments of kidney function by eGFR, proteinuria, and BP measurement. However, AKI-positive patients had higher urine concentrations of IL-18 (48.5 pg/ml versus 20.3 pg/ml [P=0.01] and 20.5 pg/ml [P<0.001]) and liver-type fatty acid-binding protein (L-FABP) (5.9 ng/ml versus 3.9 ng/ml [P=0.001] and 3.2 ng/ml [P<0.001]) than did AKI-negative patients and healthy controls. CONCLUSIONS: Novel urinary biomarkers remain elevated 7 years after an episode of CPB-AKI in children. However, there is no conventional evidence of CKD in these children. These biomarkers may be a more sensitive marker of chronic kidney injury after CPB-AKI. Future studies are needed to understand the clinical relevance of persistent elevations in IL-18, kidney injury molecule-1, and L-FABP in assessments for potential long-term kidney consequences of CPB-AKI.

Protective immunity and use of bortezomib for antibody-mediated rejection in a pediatric kidney transplant recipient.

Standard treatments for AMR-rituximab, intravenous immunoglobulin, and/or plasmapheresis-aim to suppress the production and modulate the effect of donor-specific antibodies and remove them, respectively. Proteasome inhibitors such as bortezomib are potent therapeutic agents that target plasma cells more effectively than rituximab to reduce measurable donor-specific antibody production. Little is known in adults, and no data exist in children about effects of proteasome inhibition to treat AMR on protective antibody titers. We present a pediatric renal transplant recipient who received bortezomib for relatively early AMR and whose antibody titers to measles and tetanus were tracked. The AMR was treated successfully, and we noted no clinical decrease in the overall level of protective immunity from pretransplant baseline levels at almost one yr after AMR treatment cessation. Larger studies will elucidate more clearly how proteasome inhibition to treat AMR affects protective immunity in pediatric transplant recipients.

Cystinuria: mechanisms and management.

Cystinuria is a relatively uncommon cause of pediatric stone disease, but has significant morbidity if not properly controlled because of its significant stone recurrence rate. Cystinuria is caused by the inability of the renal tubules to reabsorb filtered cystine, which is poorly soluble at a typical urine pH <7. Although many advances have been made in the understanding of the genetic and physiological basis of cystinuria, the cornerstones of treatment still involve stone prevention with dietary measures and pharmacological therapy, coupled with surgical interventions for stone removal. Pharmacological treatments can carry significant side effects that must be monitored and can limit therapy as well as impede compliance. Most patients will require surgical intervention for stone removal, although compliance with prevention strategies reduces the need for intervention.